The long-term goal of this research is development of a new treatment option for end-stage renal disease (ESRD) - a compact, wearable artificial kidney based on a new microfluidic concept. This device will provide treatment at low flow rates over long times, greatly reducing concentration and volume transient in body fluids; it may also obviate the need for anticoagulants. The key element is a primary separator that enables transport of water and solutes from the blood to a plasma-like solution (sheath fluid) without the use of a membrane. The sheath fluid carries these compounds to a secondary separator where they are transferred across a membrane to an external dialysate for disposal. The secondary separator is similar to a conventional membrane hemodialyzer or hemodiafilter, but is substantially smaller. It acts only on the sheath fluid to remove water and solutes and recycle purified sheath fluid to the primary separator. The fundamental feasibility of the primary separator of the proposed device will be proven in Phase I of this Fast-Track project, demonstrating adequate blood-cell confinement and molecular transport to a secondary (sheath) fluid. In Phase II, a succession of prototype systems comprising compatible primary and secondary separators will be developed and concurrent clinical tests performed. Patients who suffer from ESRD die without treatment. Annual costs for treatment of ESRD approach $10 billion, and market estimates indicate that almost 90% of patients are treated by hemodialysis. The device proposed here will serve the portion of that market that can be much more fully rehabilitated when freed from the regimen and deficiencies of in-clinic dialysis